Abstract
COVID-19, caused by the novel SARS-CoV-2 virus, started in China in late 2019, and soon became a global pandemic. With the help of thousands of viral genome sequences that have been accumulating, it has become possible to track the evolution of the viral genome over time as it spread across the world. An important question that still needs to be answered is whether any of the common mutations affect the viral properties, and therefore the disease characteristics. Therefore, we sought to understand the effects of mutations in RNA-dependent RNA polymerase (RdRp), particularly the common 14408C>T mutation, on mutation rate and viral spread. By focusing on mutations in the slowly evolving M or E genes, we aimed to minimize the effects of selective pressure. Our results indicate that 14408C>T mutation increases the mutation rate, while the third-most common RdRp mutation, 15324C>T, has the opposite effect. It is possible that 14408C>T mutation may have contributed to the dominance of its co-mutations in Europe and elsewhere.
Highlights
SARS-CoV-2 is a novel betacoronavirus originally identified in December 2019, and given the official name on 11 February 2020
To identify how the RNAdependent RNA polymerase (RdRp) mutations affect the mutation rate of the SARS-CoV2 genome, we examined the relationships of the RdRp mutations with mutations found in M or E proteins, in terms of both time and location
Mutation profile of SARS-CoV-2 genome as of 5 May 2020 After the low quality filters were applied, 5658 nucleotides, making up 18.9% of the SARSCoV-2 genome, were found to carry a mutation in at least one isolate, with 2668 of these sites being mutated in multiple isolates
Summary
SARS-CoV-2 is a novel betacoronavirus originally identified in December 2019, and given the official name on 11 February 2020 It is responsible for the ongoing COVID-19 pandemic, with the earliest known patients located potentially as early as November 2019, in the Hubei province of China. As a result of the origins of the disease, and due to the targeted nature of vaccine and drug discovery efforts, identifying the replication-related mutation rate and the global mutatome of SARS-CoV-2 is crucial to efforts in combating the disease. Despite having proof-reading capability, analyses of SARS-CoV-2 genomes indicated nucleotide substitution rates comparable to other RNA viruses that lack such capability[8] It is difficult to pinpoint the underlying causes without functional studies; one plausible explanation would be reduced fidelity of the main RNA polymerase, namely RNA-dependent RNA polymerase (RdRp, known as nsp12), due to mutations.
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